Glycoalkaloids in which the triglycoside portion comprises α-L-rhamnopyranosyl-(1→2gal)-O-β-D-glucopyranosyl-(1→3gal)-β-D-galactopyranose (or 6-deoxy-α-L-mannopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside) occur together with triglycoalkaloids in which the triglycoside portion is α-L-rhamnopyranosyl-(1→2glu)-O-α-L-rhamnopyranosyl-(1→4glu)-β-D-glucopyranose in plant extracts. For example, solasonine and solamargine, which occur together in the same plant extracts, are triglycoalkaloids in which the alkaloid portion is common, being solasadine, but the triglycoside portion differs. The triglycoside portion of solasonine is α-L-rhamnopyranosyl-(1→2gal)-O-β-D-glucopyranosyl-(1→3gal)-β-D-galactopyranose (or 6-deoxy-α-L-mannopyranosyl-(1→2)-O-[β-D-glucopyraonosyl-(1→13)]-β-D-galactopyranoside), whilst the triglycoside portion of solamargine is α-L-rhamnopyranosyl-(1→2glu)-O-α-L-rhamnopyranosyl-(1→4glu)-β-D-glucopyranose.
Similarly, the triglycoalkaloids α-solanine and α-chaconine occur together in plant extracts. These compounds share a common alkaloid portion, being solanidine, but, again, the triglycoside portion differs. The triglycoside portion of α-solanine is α-L-rhamnopyranosyl-(1→2gal)-O-β-D-glucopyranosyl-(1→3gal)-β-D-galactopyranose (or 6-deoxy-α-L-mannopyranosyl-(1→2)-O-[β-D-glucopyraonosyl-(1→13)]β-D-galactopyranoside), whilst the triglycoside portion of α-chaconine is α-L-rhamnopyranosyl-(1→2glu)-O-α-L-rhamnopyranosyl-(1→4glu)-β-D-glucopyranose.
Some plant extracts containing mixtures of triglycoalkaloids differing only by the triglycoside portion described above, such as plant extracts containing solasonine and solamargine, have been shown to exhibit anticancer activity. To enable thorough investigation of the activity of such compounds and to enable the manufacture of pharmaceutical products containing one of such compounds or both of such compounds in a fixed ratio, it is highly desirable to obtain the compounds in substantially pure form. However, existing methods for separation of triglycoalkaloids having an identical alkaloid portion, such as solasonine and solamargine, are time consuming and difficult to effect on any reasonable scale, meaning ‘pure’ compounds are extremely expensive.
It is one object of the present invention to provide a relatively simple method for separation of triglycoalkaloids in which the triglycoside portion comprises α-L-rhamnopyranosyl-(1→2gal)-O-β-D-glucopyranosyl-(1→3gal)-β-D-galactopyranose (or 6-deoxy-α-L-mannopyranosyl-(1→2)-O-[β-D-glucopyraonosyl-(1→3)]-β-D-galactopyranoside) from triglycoalkaloids in which the triglycoside portion is α-L-rhamnopyranosyl-(1→2glu)-O-α-L-rhamnopyranosyl-(1→4glu)-β-D-glucopyranose from a mixture containing both compounds.
Throughout this specification, unless the context requires otherwise, the word ‘separation’ when used in relation to a mixture containing both triglycoalkaloids in which the triglycoside portion comprises α-L-rhamnopyranosyl-(1→2gal)-O-β-D-glucopyranosyl-(1→3gal)-β-D-galactopyranose (or 6-deoxy-α-L-mannopyranosyl-(1→2)-O-[β-D-glucopyraonosyl-(1→3)]-β-D-galactopyranoside) and triglycoalkaloids in which the triglycoside portion is α-L-rhamnopyranosyl-(1→2glu)-O-α-L-rhamnopyranosyl-(1→4glu)-β-D-glucopyranose encompasses the enrichment of the mixture in either compound.
The preceding discussion of the background to the invention is intended to facilitate an understanding of the present invention. However, it should be appreciated that the discussion is not an acknowledgement or admission that any of the material referred to was part of the common general knowledge in Australia as at the priority date of the application.
Throughout the specification, unless the context requires otherwise, the word “comprise” or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
Throughout this specification, unless the context specifies otherwise, reference to solamargine includes both the free base and solamargine salts, and reference to solasonine includes both the free base and solasonine salts.
Throughout this specification, unless the context requires otherwise, a triglycoalkaloid having a triglycoside portion comprising α-L-rhamnopyranosyl-(1→2gal)-O-β-D-glucopyranosyl-(1→3gal)-β-D-galactopyranose (or 6-deoxy-α-L-mannopyranosyl-(1→2)-O-[β-D-glucopyraonosyl-(1→3)]-β-D-galactopyranoside), such as solasonine, will be referred to as a ‘rhamnose-glucose-galactose triglycoalkaloid’, whilst a triglycoalkaloid having a triglycoside portion comprising α-L-rhamnopyranosyl-(1→2glu)-O-α-L-rhamnopyranosyl-(1→4glu)-β-D-glucopyranose, such as solamargine, will be referred to as a ‘rhamnose-rhamnose-glucose triglycoalkaloid’.